tbuckley/cabot-search huggingface dataset:
Endoscopic ultrasound-guided fine-needle biopsy with or without macroscopic on-site evaluation: a randomized controlled noninferiority trial
Authors: Benedetto Mangiavillano, Stefano Francesco Crinò, Antonio Facciorusso, Francesco Di Matteo, Carmelo Barbera, Alberto Larghi, Gianenrico Rizzatti, Silvia Carrara, Marco Spadaccini, Francesco Auriemma, Carlo Fabbri, Cecilia Binda, Chiara Coluccio, Gianmarco Marocchi, Teresa Staiano, Maria Cristina Conti Bellocchi, Laura Bernardoni, Leonardo Henri Eusebi, Giovanna Grazia Cirota, Germana De Nucci, Serena Stigliano, Gianpiero Manes, Giacomo Bonanno, Andrew Ofosu, Laura Lamonaca, Danilo Paduano, Federica Spatola, Alessandro Repici
Journal: Endoscopy (2022)

Background The advantage of using the macroscopic on-site evaluation (MOSE) technique during endoscopic ultrasound-guided fine-needle biopsy (EUS-FNB) performed with 22G Franseen needles has not been investigated. We aimed to compare EUS-FNB with MOSE vs. EUS-FNB performed with three needle passes. Methods This randomized trial involved 10 Italian referral centers. Consecutive patients referred for EUS-FNB of pancreatic or nonpancreatic solid lesions were included in the study and randomized to the two groups. MOSE was performed by gross visualization of the collected material by the endoscopists and considered adequate when a white/yellowish aggregate core longer than 10 mm was retrieved. The primary outcome was diagnostic accuracy. Secondary outcomes were specimen adequacy, number of needle passes, and safety. Results 370 patients with 234 pancreatic lesions (63.2 %) and 136 nonpancreatic lesions (36.8 %) were randomized (190 EUS-FNB with MOSE and 180 with standard EUS-FNB). No statistically significant differences were found between EUS-FNB with MOSE and conventional EUS-FNB in terms of diagnostic accuracy (90.0 % [95 %CI 84.8 %–93.9 %] vs. 87.8 % [95 %CI 82.1 %–92.2 %]; P = 0.49), sample adequacy (93.1 % [95 %CI 88.6 %–96.3 %] vs. 95.5 % [95 %CI 91.4 %–98 %]; P = 0.31), and rate of adverse events (2.6 % vs. 1.1 %; P = 0.28). The median number of passes was significantly lower in the EUS-FNB with MOSE group (1 vs. 3; P &lt; 0.001). Conclusions The accuracy of EUS-FNB with MOSE is noninferior to that of EUS-FNB with three needle passes. MOSE reliably assesses sample adequacy and reduces the number of needle passes required to obtain the diagnosis with a 22G Franseen needle.
Modified Eligibility Criteria: Patient Access and Subpopulation Applicability vs Efficiency in Drug Development
Authors: Peter J O’Dwyer
Journal: JNCI Journal of the National Cancer Institute (2022)

For more than 10 years now, clinical trials experts have been convened by the American Society of Clinical Oncology (ASCO) with Friends of Cancer Research (FOCR), along with input from the US Food and Drug Administration, to develop consensus surrounding barriers to patient participation in cancer clinical trials.The original scope of this effort was to improve patient access to clinical trials, in the expectation that the generalizability of the data would be enhanced as a result (1).Clinical trial participation at the time was stuck at an estimated 3%-4% (2), a value that had not changed materially in 20 years (3).Data from several analyses (3-5) suggested that an inability to meet overly restrictive eligibility criteria was limiting patient access to promising new therapies, prolonging accrual to trials, and delaying progress.In 2017, the ASCO-FOCR collaboration (1) suggested that modifications to 5 of the commonly used eligibility criteria could broaden access: exclusion of patients with brain metastases, minimum age of 18 years, known HIV status, indices of renal or hepatic function, and history of prior or concurrent malignancy.In response, in 2018 the Cancer Therapy Evaluation Program elaborated templated language to address these criteria, such that trials supported by National Institutes of Health funding would adopt this language.In this issue of the Journal, Denicoff and colleagues (6) have evaluated 122 protocols mainly from the National Clinical Trials Network (n ¼ 69 trials) and the Experimental Therapeutics Network (n ¼ 44 trials) for their adherence to the new language.Their analysis adds valuable insight to the practical aspects of implementing sweeping changes to structures that have evolved over some 50 years and points to several areas that argue for more robust approaches to achieving consensus.The data are striking at first glance in that adoption of the recommendations is quite heterogeneous.Liberalizing hepatic and renal criteria characterized 86% of protocols, and prohibition of patients living with HIV had been removed in 76%.The authors rightly interpret this as a low number, given substantial evidence to support favorable outcomes in HIV-infected patients on appropriate antiretroviral therapy (7).Other criteria were even more poorly supported: restriction on prior cancers removed in 66%, controlled brain metastases in 51%, and age (down to age 12 years or older) in just 50% of a small sample.
Detection of <i>Klebsiella pneumoniae</i> human gut carriage: a comparison of culture, qPCR, and whole metagenomic sequencing methods
Authors: Kenneth Lindstedt, Dorota Buczek, Torunn Pedersen, Erik Hjerde, Niclas Raffelsberger, Yutaka Suzuki, Sylvain Brisse, Kathryn Holt, Ørjan Samuelsen, Arnfinn Sundsfjord
Journal: Gut Microbes (2022)

Klebsiella pneumoniae is an important opportunistic healthcare-associated pathogen and major contributor to the global spread of antimicrobial resistance. Gastrointestinal colonization with K. pneumoniae is a major predisposing risk factor for infection and forms an important hub for the dispersal of resistance. Current culture-based detection methods are time consuming, give limited intra-sample abundance and strain diversity information, and have uncertain sensitivity. Here we investigated the presence and abundance of K. pneumoniae at the species and strain level within fecal samples from 103 community-based adults by qPCR and whole metagenomic sequencing (WMS) compared to culture-based detection. qPCR demonstrated the highest sensitivity, detecting K. pneumoniae in 61.2% and 75.8% of direct-fecal and culture-enriched sweep samples, respectively, including 52/52 culture-positive samples. WMS displayed lower sensitivity, detecting K. pneumoniae in 71.2% of culture-positive fecal samples at a 0.01% abundance cutoff, and was inclined to false positives in proportion to the relative abundance of other Enterobacterales present. qPCR accurately quantified K. pneumoniae to 16 genome copies/reaction while WMS could estimate relative abundance to at least 0.01%. Quantification by both methods correlated strongly with each other (Spearman's rho = 0.91). WMS also supported accurate intra-sample K. pneumoniae sequence type (ST)-level diversity detection from fecal microbiomes to 0.1% relative abundance, agreeing with the culture-based detected ST in 16/19 samples. Our results show that qPCR and WMS are sensitive and reliable tools for detection, quantification, and strain analysis of K. pneumoniae from fecal samples with potential to support infection control and enhance insights in K. pneumoniae gastrointestinal ecology.
Bezlotoxumab prevents extraintestinal organ damage induced by <i>Clostridioides difficile</i> infection
Authors: Steven J. Mileto, Melanie L. Hutton, Sarah L. Walton, Antariksh Das, Lisa J. Ioannidis, Don Ketagoda, Kylie M. Quinn, Kate M. Denton, Diana S. Hansen, Dena Lyras
Journal: Gut Microbes (2022)

Clostridioides difficile is the most common cause of infectious antibiotic-associated diarrhea, with disease mediated by two major toxins TcdA and TcdB. In severe cases, systemic disease complications may arise, resulting in fatal disease. Systemic disease in animal models has been described, with thymic damage an observable consequence of severe disease in mice. Using a mouse model of C. difficile infection, we examined this disease phenotype, focussing on the thymus and serum markers of systemic disease. The efficacy of bezlotoxumab, a monoclonal TcdB therapeutic, to prevent toxin mediated systemic disease complications was also examined. C. difficile infection causes toxin-dependent thymic damage and CD4+CD8+ thymocyte depletion in mice. These systemic complications coincide with changes in biochemical markers of liver and kidney function, including increased serum urea and creatinine, and hypoglycemia. Administration of bezlotoxumab during C. difficile infection prevents systemic disease and thymic atrophy, without blocking gut damage, suggesting the leakage of gut contents into circulation may influence systemic disease. As the thymus has such a crucial role in T cell production and immune system development, these findings may have important implications in relapse of C. difficile disease and impaired immunity during C. difficile infection. The prevention of thymic atrophy and reduced systemic response following bezlotoxumab treatment, without altering colonic damage, highlights the importance of systemic disease in C. difficile infection, and provides new insights into the mechanism of action for this therapeutic.Abbreviations: Acute kidney injury (AKI); Alanine Transaminase (ALT); Aspartate Aminotransferase (AST); C. difficile infection (CDI); chronic kidney disease (CKD); combined repetitive oligo-peptides (CROPS); cardiovascular disease (CVD); Double positive (DP); hematoxylin and eosin (H&E); immunohistochemical (IHC); multiple organ dysfunction syndrome (MODS); phosphate buffered saline (PBS); standard error of the mean (SEM); surface layer proteins (SLP); Single positive (SP); wild-type (WT).
An Acellular Scaffold Facilitates Endometrial Regeneration and Fertility Restoration via Recruiting Endogenous Mesenchymal Stem Cells
Authors: Liaobing Xin, Xiaowen Zheng, Jianmin Chen, Sentao Hu, Yilun Luo, Qunzi Ge, Xiaoying Jin, Lie Ma, Songying Zhang
Journal: Advanced Healthcare Materials (2022)

Abstract Severe intrauterine adhesions (IUAs), characterized by inadequate endometrial repair and fibrosis, can lead to infertility. Stem cell‐based therapies, which deliver mesenchymal stem cells (MSCs) to the wound site, hold a considerable promise for endometrium regeneration. However, some notable hurdles, such as stemness loss, immunogenicity, low retention and survival rate, limit their clinical application. Evidence shows a strategy of mobilizing endogenous MSCs recruitment can overcome the traditional limitations of exogenous stem cell‐based therapies. Here, an acellular biomaterial named stromal derived factor‐1 alpha (SDF‐1 α )/E7‐modified collagen scaffold (CES) is explored. CES based on harnessing the innate regenerative potential of the body enables near‐complete endometrium regeneration and fertility restoration both in a rat endometrium acute damage model and a rat IUA model. Mechanistically, the CES implantation promotes endogenous MSCs recruitment via a macrophage‐coordinated strategy; then the homing MSCs exert the function of immunomodulation and altered local microenvironments toward regeneration. To conclude, CES, which can harness endogenous MSCs and overcome the traditional limitations of cell‐based therapies, can serve as a clinically feasible and cell‐free strategy with high therapeutic efficiency for IUA treatment.
Learning curve for esophageal peroral endoscopic myotomy: a systematic review and meta-analysis
Authors: Srinivas R. Puli, Mihir S. Wagh, David Forcione, Harishankar Gopakumar
Journal: Endoscopy (2022)

Background and study aims Peroral endoscopic myotomy (POEM) is a minimally invasive endoscopic procedure for the treatment of achalasia and certain spastic esophageal motility disorders, delivering excellent results in experienced hands. However, this complex and technically challenging procedure requires advanced endoscopic skills. The aim of this study was to conduct a systematic review and meta-analysis of current data to evaluate the learning curve for POEM in new adopters of this technique. Methods Electronic databases (PubMed, Embase, and Cochrane Library) from inception to November 2021 were searched for publications addressing the learning curve in POEM. Pooling was conducted by both fixed- and random-effects models. Secondary outcomes reviewed were clinical success defined by Eckardt score ≤ 3 when available and adverse events. Results Eight studies involving 1904 patients met the inclusion criteria. In the pooled analysis, new adopters of POEM attained proficiency at a mean of 24.67 procedures (95 %CI 23.93 to 25.41). Once proficiency was achieved, the pooled total procedure time plateaued at a mean of 85.38 minutes (95 %CI 81.48 to 89.28), the pooled mean procedure time per centimeter of myotomy was 6.25 minutes (95 %CI 5.69 to 6.82), and the pooled mean length of myotomy was 11.49 cm (95 %CI 10.90 to 12.08). Conclusions Our analysis showed that new adopters of POEM with previous advanced endoscopy experience required about 25 procedures to attain proficiency. The average time for each procedure once proficiency was attained was about 85 minutes.
Masquelet technique in military practice: specificities and future directions for combat-related bone defect reconstruction
Authors: Laurent Mathieu, Romain Mourtialon, Marjorie Durand, Arnaud de Rousiers, Nicolas de l’Escalopier, Jean-Marc Collombet
Journal: Military Medical Research (2022)

Because of its simplicity, reliability, and replicability, the Masquelet induced membrane technique (IMT) has become one of the preferred methods for critical bone defect reconstruction in extremities. Although it is now used worldwide, few studies have been published about IMT in military practice. Bone reconstruction is particularly challenging in this context of care due to extensive soft-tissue injury, early wound infection, and even delayed management in austere conditions. Based on our clinical expertise, recent research, and a literature analysis, this narrative review provides an overview of the IMT application to combat-related bone defects. It presents technical specificities and future developments aiming to optimize IMT outcomes, including for the management of massive multi-tissue defects or bone reconstruction performed in the field with limited resources.
Outpatient Photodynamic Diagnosis–guided Laser Destruction of Bladder Tumors Is as Good as Conventional Inpatient Photodynamic Diagnosis–guided Transurethral Tumor Resection in Patients with Recurrent Intermediate-risk Low-grade Ta Bladder Tumors. A Prospective Randomized Noninferiority Clinical Trial
Authors: Gyrithe Lynghøj Pedersen, Marie Schmidt Erikson, Karin Mogensen, Susanne Rosthøj, Gregers Gautier Hermann
Journal: European Urology (2022)
The Tumor Microenvironment Represses T Cell Mitochondrial Biogenesis to Drive Intratumoral T Cell Metabolic Insufficiency and Dysfunction
Authors: Nicole E. Scharping, Ashley V. Menk, Rebecca S. Moreci, Ryan D. Whetstone, Rebekah E. Dadey, Simon C. Watkins, Robert L. Ferris, Greg M. Delgoffe
Journal: Immunity (2016)
The Challenges of Emerging Infectious Diseases
Authors: Fred C. Tenover
Journal: JAMA (1996)

THE LIST of emerging infectious diseases is an intriguing constellation of new entities (a previously unrecognized<i>Hantavirus</i>), recognized pathogens that have caused recent outbreaks of unprecedented size (<i>Cryptosporidium</i>in municipal water supplies), outbreaks that have culminated in a reassessment of the issue of food safety (<i>Escherichia coli</i>O157:H7), and traditional nosocomial and community-acquired infections that, due to their resistance to multiple antimicrobial agents, have suggested the possibility of a postantibiotic era.<sup>1,2</sup><i>Enterococcus faecium, Streptococcus pneumoniae</i>, and<i>Mycobacterium tuberculosis</i>are just a few of the organisms that have become considerably more difficult to treat due to increasing drug resistance. Examples of the types of resistant bacteria that have emerged around the world are shown in Figure 1, while specific examples of emerging resistance problems in the United States are shown in Figure 2. Clearly, the emergence of resistant organisms has been a global phenomenon. A recent Institute of Medicine report
Evaluation of Dressing Regimens for Prevention of Infection With Peripheral Intravenous Catheters
Authors: Dennis G. Maki
Journal: JAMA (1987)

Four dressing regimens for peripheral venous catheters were studied in a prospective randomized clinical trial with 2088 Teflon catheters: (1) sterile gauze, replaced every other day, and three dressings left on for the lifetime of the catheter; (2) gauze; (3) a transparent polyurethane dressing; and (4) an iodophor-transparent dressing. The four dressings provided comparable coverage, except moisture accumulated more frequently under the transparent dressings 26% to 28% vs 20% to 21% Cutaneous colonization under the dressing was low level and comparable with all four dressings (range, 100.58 to 100.70 colony-forming units). The rate of local catheter-related infection ≥15 colony-forming units) was also low and did not differ significantly (range, 4.6% to 5.9%); no catheter caused bacteremia. Stepwise logistic multivariate analysis showed cutaneous colonization of the insertion site (relative risk [RR] of infection, 3.86), contamination of the catheter hub (RR, 3.78), moisture under the dressing (RR, 2.48), and prolonged catheterization (RR, 1.75) to be significant risk factors for catheter-related infection. These data indicate that it is not cost-effective to redress peripheral venous catheters at periodic intervals; for most patients, either sterile gauze or a transparent dressing can be used and left on until the catheter is removed. (<i>JAMA</i>1987;258:2396-2403)
Living Longer, Aging Better
Authors: Terrie Wetle
Journal: JAMA (1997)

The study of aging is not what it used to be. In 1974, when the National Institute on Aging (NIA) was created as part of the National Institutes of Health, gerontology was a young science. Rich in hypotheses but poor in data, gerontology lacked, or was just in the early stages of developing, ways to explore the fundamentals of the aging process. Knowledge of aging clustered around specific diseases associated with advancing age; indeed, it was widely believed that aging was equated with decline and illness. Now, nearly 25 years later, the science base has grown in depth, breadth, and detail. And with this growth have come new insights into the secrets of aging. This theme issue ofThe Journalillustrates the ongoing maturation of aging research. The articles in this issue span a wide range of questions and methods currently used in gerontology and geriatrics research, including an analysis
Telomere biology disorders: time for moving towards the clinic?
Authors: Luis F.Z. Batista, Inderjeet Dokal, Roy Parker
Journal: Trends in Molecular Medicine (2022)

Telomere biology disorders (TBDs) are a group of rare diseases caused by mutations that impair telomere maintenance. Mutations that cause reduced levels of TERC/hTR, the telomerase RNA component, are found in most TBD patients and include loss-of-function mutations in hTR itself, in hTR-binding proteins [NOP10, NHP2, NAF1, ZCCHC8, and dyskerin (DKC1)], and in proteins required for hTR processing (PARN). These patients show diverse clinical presentations that most commonly include bone marrow failure (BMF)/aplastic anemia (AA), pulmonary fibrosis, and liver cirrhosis. There are no curative therapies for TBD patients. An understanding of hTR biogenesis, maturation, and degradation has identified pathways and pharmacological agents targeting the poly(A) polymerase PAPD5, which adds 3'-oligoadenosine tails to hTR to promote hTR degradation, and TGS1, which modifies the 5'-cap structure of hTR to enhance degradation, as possible therapeutic approaches. Critical next steps will be clinical trials to establish the effectiveness and potential side effects of these compounds in TBD patients.
Letter to the editor: In utero exposure to mercury is associated with increased susceptibility to liver injury and inflammation in childhood
Authors: Muhammad Zawar Asif, Muhammad Umair, Muhammad Shehryar
Journal: Hepatology (2022)

To the editor, We read Stratakis et al.'s1 study "In Utero Exposure to Mercury is Associated With Increased Susceptibility to Liver Injury and Inflammation in Childhood" with great interest. The authors worked hard on this succinct, informative manuscript. We agree that mercury exposure during childhood can cause inflammation and NAFLD. The study helps us comprehend the impact of early life environmental exposures in the NAFLD epidemic. Strategies to minimize mercury pollution and early life exposure may prevent NAFLD in children. We feel compelled to highlight concerns that would have enhanced this study's quality and results. Firstly, retrospective studies involve issues because of recollection bias and poor patient documentation, which may have been avoided if the authors included cases from the more current period. Second, pregnant mothers and newborns were not described. A 2017 study by Huang et al.2 covered height, prepregnancy weight, birth weight, birth length, birth head circumference, birth chest circumference, and gestational age at birth. The authors did not report prevalent comorbidities in the study population, which could have changed the results. Another 2017 study by Choi et al.3 classified hypertension, diabetes, renal disease, dyslipidemia, tuberculosis, and hepatitis B. In the baseline survey, fish intake should have been analyzed using the 24 h food recall approach, incorporating multiple mercury‐related variables. The 24 h diet recall should have captured two nonconsecutive days' diet and averaged food group consumption (g/kg/d). Fish consumption could confuse connections between plasma mercury and liver function. Eighty to ninety percent of the human body's organic mercury is derived from fish and shellfish consumption. Fish eating raises total blood mercury levels; however, the antioxidant properties of fish oil and minerals may mitigate the toxicity of mercury on liver enzymes. Most previous research has not investigated fish consumption in depth. A more recent epidemiological study by Mergler focused on linear associations or mercury levels divided into quantiles, which could lead to skewed results if these factors are correlated.4 Because the fetal brain is so sensitive to mercury poisoning, government and international organizations use it to evaluate risk. The most informative picture of exposure is obtained from both biomarkers, along with fish consumption and other dietary data.4
L-buthionine sulfoximine encapsulated hollow calcium peroxide as a chloroperoxidase nanocarrier for enhanced enzyme dynamic therapy
Authors: Bin Liu, Yulong Bian, Meng Yuan, Yanlin Zhu, Shikai Liu, He Ding, Shili Gai, Piaoping Yang, Ziyong Cheng, Jun Lin
Journal: Biomaterials (2022)